The long-term goals are to understand better the different hemodynamic and metabolic changes that occur during chronic heart failure (CHF) and how these changes are related to changes in physical work capacity. Patients with CHF are characterized with a diminished capacity to perform physical work. However, patients who participate in a program of dynamic exercise training or who receive chronic renin-angiotensin converting enzyme (ACE) inhibitory therapy have shown increases in work capacity as indicated by increases in either work duration, work rate, or maximal oxygen consumption (VO2 max). The mechanisms which account for these increases in work capacity are not completely understood. Patients with CHF who receive chronic ACE inhibitory therapy demonstrate increases in work capacity which are highly correlated with increases in left ventricular pump function. However, patients with CHF who participate in a program of dynamic exercise training demonstrate increases in work capacity without any changes in left ventricular pump function. These data suggest that with chronic ACE inhibitory therapy, that the increases in work capacity are related, in part, to an increased ability to deliver oxygen to the working skeletal muscles, whereas with training, this may not be true. In fact, the data also strongly suggests that with dynamic exercise training that the increases in work capacity may be related, in part, to specific biochemical adaptations within the skeletal muscles themselves. The specific aims of this research project are: (a) to determine the mechanisms which account for these increases in work capacity; and (b) to determine whether a program of training and long-term ACE inhibitory therapy have a complementary effect on work capacity. This will be accomplished in a rat model in which CHF is induced by coronary artery ligation. The principal investigator has preliminary data demonstrating that exercise trained CHF rats have a greater VO2 max than their sedentary counterparts. In the first group of proposed studies, the mechanisms which account for these increases in VO2 max will be delineated. In the second group of experiments, increases in VO2 max due to chronic ACE inhibitory therapy will be investigated and again the underlying mechanisms delineated. Finally, CHF rats which participate in an exercise training program while simultaneously receiving chronic ACE inhibitory therapy will be investigated and it will be determined whether these two types of therapy for CHF are complementary in nature as indicated by increases in VO2 max and by the mechanisms involved which account for these increases.